The specific aim of the proposed research is to continue to develop the analytical capability of 252Cf-plasma desorption mass spectrometry for biomedical research involving large biomolecules (m/z greater than 5000). Part of the plan is to change the method of sample preparation so that the formation of molecular ions from the substrate will be less dependent on matrix effects and at the same time will improve sensitivity to the picomole level. The new method of sample preparation will utilize adsorption of proteins (insulin and cytochrome-C) onto polymeric surfaces from liquid solutions. The interaction will be analyzed using phase equilibrium thermodynamics to evaluate equilibrium constants, DeltaH, and DeltaS for adsorption. These same surfaces will become samples for 252Cf-PDMS analysis. Fractional coverage will be determined by 252Cf-PDMS. A general study of polymer-protein surface thermodynamics will be carried out using 252Cf-PDMS as an analytical method. Two important protein systems, interferon and hemoglobin, have been targeted as the next model compounds for extending the mass range and capabilities of 252Cf-PDMS. Some feasibility studies will be carried out to determine whether 252Cf-PDMS might be used to study antibody-antigen interactions and receptor sites on cell surfaces. The studies of protein-polymer interactions have relevance to the genesis of atherosclerosis. Specific interactions between proteins and receptor sites are fundamental to the immune response in humans and in understanding the role of proteins such as insulin in triggering a response within a cell when it attaches to a receptor site.